Fmoc-O-t-butyl-L-serine-N-hydroxysuccinimide ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-O-t-butyl-L-serine-N-hydroxysuccinimide ester
• 英文别名: Fmoc-L-Ser(O-t-butyl)-NHSE；FmocSer(Bu-t)OSu；Fmoc-L-Ser(tBu)-OSu；Fmoc-L-(O-tert-butyl)serine N-hydroxysuccinimide ester；Fmoc-ser(tbu)-osu；(2,5-dioxopyrrolidin-1-yl) (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoate
• 化学式: C₂₆H₂₈N₂O₇
• 分子量: 480.518
• InChiKey: YMIOGYMVKNEIPY-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Fmoc-O-t-butyl-L-serine-N-hydroxysuccinimide ester 在 1-羟基苯并三唑 、 氧-17原子 作用下， 以 四氢呋喃 为溶剂， 反应 120.0h， 生成 FMOC-O-叔丁基-L-丝氨酸
  参考文献：
  名称：

  EP1757568

  摘要：

  公开号：
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 FMOC-O-叔丁基-L-丝氨酸 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 Fmoc-O-t-butyl-L-serine-N-hydroxysuccinimide ester
  参考文献：
  名称：

  通过固相肽合成将多个硫酰胺取代基位点特异性结合到肽主链中。

  摘要：

  在各种肽修饰策略中，通过用硫原子取代酰胺键的羰基氧原子进行硫酰胺取代，对于化学生物学而言是不可估量的工具，可用于肽药物发现和蛋白质结构功能研究。然而，由于缺乏用于位点特异性地将硫酰胺键结合到肽主链中，特别是将多个硫酰胺取代引入到固体支持物上的肽的合成方法，所以尚未对硫酰胺取代作用进行很好的研究。在此，我们报告了一种高效的方法，该方法通过使用α-硫代酰氧基烯酰胺（通过添加N保护的单硫代氨基酸和乙酰胺形成）以位点特异性的方式将硫酰胺键结合到肽主链中，作为固相肽合成中的新型硫酰化试剂。此方法适用于20个蛋白原氨基酸中的19个，His是一个例外。可以将一个至多个硫酰胺取代基掺入正在生长的肽中，而没有差向异构化或低水平的差向异构化。通过使用该方法，可以平滑地合成包含多达五个连续硫代酰胺键的完全硫代酰胺取代的六肽。这种合成方法将刺激硫酰胺取代工具在蛋白质工程和肽药物发现中的应用。可以顺利合成含多达五个

  DOI：

  10.1021/acs.joc.9b02486

文献信息

• Discovery of a New Phosphotyrosine Mimetic for PTP1B Using Breakaway Tethering
  作者：Daniel A. Erlanson、Robert S. McDowell、Molly M. He、Mike Randal、Robert L. Simmons、Jenny Kung、Andrew Waight、Stig K. Hansen

  DOI：10.1021/ja034440c

  日期：2003.5.1

  both a masked thiol and a known pY mimetic. The extender is then cleaved to release the pY mimetic, unmasking the thiol. The resulting protein is screened against a library of disulfide-containing small molecule fragments; any molecules with inherent affinity for the pY binding site will preferentially form disulfides with the extender, allowing for their identification by mass spectrometry. The ability

  蛋白质酪氨酸磷酸酶在涉及人类疾病的许多信号级联反应中发挥重要作用。鉴定这些靶标的类药物抑制剂是一项重大挑战，而发现合适的磷酸酪氨酸 (pY) 模拟物仍然是主要困难之一。在这里，我们描述了网络共享技术的扩展，“分离网络共享”，它非常适合发现这种新的化学实体。该方法首先涉及使用包含掩蔽硫醇和已知 pY 模拟物的扩展剂不可逆地修饰蛋白质。然后将扩展剂裂解以释放 pY 模拟物，暴露硫醇。得到的蛋白质针对含有二硫键的小分子片段文库进行筛选；任何对 pY 结合位点具有内在亲和力的分子将优先与扩展剂形成二硫化物，从而可以通过质谱法对其进行鉴定。从已知底物开始的能力最大限度地减少了蛋白质结构的扰动，并增加了使用束缚探测活性位点的机会。我们将这种方法应用于抗糖尿病蛋白 PTP1B，以发现一种 pY 模拟物，它属于一个新的分子类别并以一种新的方式结合。
• Trimethylsilylnitrate−Trimethylsilyl Azide:  A Novel Reagent System for the Synthesis of 2-Deoxyglycosyl Azides from Glycals. Application in the Synthesis of 2-Deoxy-β-<i>N</i>-glycopeptides
  作者：B. Gopal Reddy、K. P. Madhusudanan、Yashwant D. Vankar

  DOI：10.1021/jo0354948

  日期：2004.4.1

  1-azido 2-deoxy sugars in one step in fair to good yields. Galactals offer higher stereoselectivities than do the glucals. Reduction of the azide group with Ph3P−H2O to amino functionality followed by coupling with amino acids leads to the synthesis of novel 2-deoxy-β-N-glycopeptides irrespective of the geometry of initial azido sugars. Using this protocol, a new γ-sugar amino acid derivative is also procured

  包含Me 3 SiN 3和20mol％的Me 3 SiONO 2的新型试剂系统允许在一个步骤中将糖类转化为1-叠氮基2-脱氧糖，以公平至良好的产率。与葡萄糖相比，半乳糖具有更高的立体选择性。与初始叠氮糖的几何结构无关，用Ph 3 P-H 2 O将叠氮化物基团还原为氨基官能团，然后与氨基酸偶联可导致合成新型2-脱氧-β - N-糖肽。使用该协议，还可以购买新的γ-糖氨基酸衍生物。
• METHOD OF LABELING WITH ISOTOPE OF OXYGEN
  申请人：Riken

  公开号：EP1757568A1

  公开（公告）日：2007-02-28

  The present invention provides methods for labeling one or two oxygen atom(s) in a carboxyl group of a carboxyl-containing compound with an oxygen isotope selected from oxygen-17 (17O) or oxygen-18 (18O). The methods of the present invention are characterized in that an activated ester of the carboxyl-containing compound (carboxylic acid) is reacted with H217O or H218O in the presence of an activator. In the methods of the present invention, the reaction between the activated ester of a carboxylic acid and H217O or H218O can be allowed to proceed without including drastic conditions such as strongly acidic conditions or alkaline hydrolysis because an activator is used.

  本发明提供了用选自氧-17（17O）或氧-18（18O）的氧同位素标记含羧基化合物羧基中的一个或两个氧原子的方法。本发明方法的特征在于，含羧基化合物（羧酸）的活化酯在活化剂存在下与 H217O 或 H218O 反应。在本发明的方法中，由于使用了活化剂，羧酸的活化酯与 H217O 或 H218O 之间的反应可以在不包括强酸性条件或碱性水解等剧烈条件下进行。
• Synthetic approaches to peptides containing the l-Gln-l-Val-D(S)-Dmt motif
  作者：Ghadeer A.R.Y. Suaifan、Tawfiq Arafat、Michael D. Threadgill

  DOI：10.1016/j.bmc.2007.03.005

  日期：2007.5

  The pseudoprolines S-Dmo (5,5-dimethyl-4-oxaproline) and R-Dmt (5,5-dimethyl-4-thiaproline) have been used to study the effects of forcing a fully cis conformation in peptides. Synthesis of peptides containing these (which have the same configuration as L-Pro) is straightforward. However, synthesis of peptides containing S-Dmt is difficult, owing to the rapid cyclisation of L-Aaa-S-Dmt amides and esters to form the corresponding diketopiperazines (DKP); thus the intermediacy Of L-Aaa-S-Dmt amides and esters must be avoided in the synthetic sequence. Peptides containing the L-Gln-L-Val-D(S)-Dmt motif are particularly difficult, owing to the insolubility of coupling partners containing Gln. Introduction of Gln as N-Boc-pyroglutamate overcame the latter difficulty and the dipeptide active ester BocPygValOC(6)F(5) coupled in good yield with S-DmtOH. BocPygVal-SDmtNH(CH2)(2)C6H4NO2 was converted quantitatively to BocGlnVal-S-DmtNH(CH2)(2)C6H4NO2 with ammonia, demonstrating the utility of this approach. Two peptide derivatives (CbzSerLysLeuGInVal-S-DmtNH(CH2)(2)C6H4NO2 and CbzSerSerLysLeuGInVal-S- DmtNH(CH2)(2)C6H4NO2) were assembled, using these new methods of coupling a dipeptide acid active ester with S-DmtOH and introduction of Gin as Pyg, followed by conventional peptide couplings. The presence of the Val caused these peptides to be cleaved very slowly by prostate-specific antigen (PSA) at Len down arrow Gln, rather than the expected Gln down arrow Val. (c) 2007 Elsevier Ltd. All rights reserved.
• Adenosine analogs bearing phosphate isosteres as human MDO1 ligands
  作者：Yuezhou Zhang、Mikael Jumppanen、Mirko M. Maksimainen、Samuli Auno、Zulfa Awol、Léo Ghemtio、Harikanth Venkannagari、Lari Lehtiö、Jari Yli-Kauhaluoma、Henri Xhaard、Gustav Boije af Gennäs

  DOI：10.1016/j.bmc.2018.02.006

  日期：2018.5

  The human O-acetyl-ADP-ribose deacetylase MDO1 is a mono-ADP-ribosylhydrolase involved in the reversal of post-translational modifications. Until now MDO1 has been poorly characterized, partly since no ligand is known besides adenosine nucleotides. Here, we synthesized thirteen compounds retaining the adenosine moiety and bearing bioisosteric replacements of the phosphate at the ribose 50-oxygen. These compounds are composed of either a squaryldiamide or an amide group as the bioisosteric replacement and/or as a linker. To these groups a variety of substituents were attached such as phenyl, benzyl, pyridyl, carboxyl, hydroxy and tetrazolyl. Biochemical evaluation showed that two compounds, one from both series, inhibited ADP-ribosyl hydrolysis mediated by MDO1 in high concentrations. (C) 2018 Elsevier Ltd. All rights reserved.